1. Technical Field of the Invention
The present invention relates to the formulation of active principles into pharmaceutical compositions useful for topical pharmaceutical applications.
The present invention relates more particularly to stable anhydrous pharmaceutical compositions comprising a silicone agent and, as bioaffecting active principles, vitamin D or a vitamin D derivative and a corticosteroid, to the process for preparing same and to administration thereof for the topical treatment of psoriasis and other skin disorders.
2. Description of Background and/or Related and/or Prior Art
Vitamin D and its derivatives are generally used in dermatology in the treatment of psoriasis since they limit the excessive production of cutaneous cells on the surfaces affected and possess proven advantages for the treatment of this ailment, which is characterized in particular by the presence of thick, squamous and dry lesions.
It is known that a certain number of active principles which exhibit advantageous therapeutic activity are sensitive to oxidation and in particular undergo chemical degradation leading to a substantial loss in their activity in the presence of water.
The combination in a single pharmaceutical composition of vitamin D or a vitamin D derivative with a corticosteroid is not without its problems. This is because vitamin D or some vitamin D derivatives are unstable in an acidic environment (they have maximum stability at pH values of approximately 8) and certain corticosteroids are unstable in a basic environment (they exhibit maximum stability at a pH of approximately 4 to 6).
Consequently, it is appropriate to formulate these active principles in anhydrous compositions.
The anhydrous compositions presently available on the market which allow the formulation of water-sensitive active principles while ensuring their effective chemical stability are generally ointment compositions. These ointment compositions are composed principally of petroleum jelly, mineral oil and/or vegetable oil. Certain of the compositions comprising petroleum jelly, however, are considered after application to be sticky and greasy, and in addition are shiny. The greasy residue left on the skin prevents the patient afflicted by psoriasis from putting on his or her clothes again after treatment without the risk of leaving greasy marks thereon, which does not necessarily encourage the patient to follow his or her treatment. Non-compliance with the prescribed treatment is one of the main causes of failure; the article “Patients with psoriasis and their compliance with medication, Richards et al., J. Am. Acad. Dermatol., October 1999, pp. 581-583” indicates that almost 40% of patients with a chronic disease such as psoriasis do not follow their treatment. The characteristics of the vehicle used in the pharmaceutical compositions are directly linked to the adherence by the patient to his or her treatment.
The ointment compositions presently on the market do not always lend themselves to the formulation of the active principle in a solubilized form.
EP-0,255,369 and U.S. Pat. No. 6,103,250 describe formulations based for the most part on silicone derivatives, in which the water-sensitive active substances are formulated in a dispersed form. The dispersed form, however, is generally detrimental to optimum skin penetration and/or release of these active substances.